Apical fibrobullous lung disease in spondyloarthritis patients with biologic DMARDs indication.

OBJECTIVE: The rate of pleuroparenchymal involvement in patients with SpA varies widely, from 0% to 85%. The most common form is apical fibrobullous disease (AFLD). The aim of this study was to determine the incidence of AFLD and associated factors in SpA patients under and/or planned to start biologic DMARDs (bDMARDs) therapy. METHODS: The records of 3021 SPA patients registered with HUR-BIO who had indication of bDMARDs between 2010 and 2021 were scanned. The study included 2489 patients with at least one chest radiograph (X-ray). Patient demographics, comorbidities, laboratory data, bDMARDs used, baseline DASs, and purified protein derivative and/or QuantiFERON test results before initiation of bDMARDs were recorded. RESULTS: Of the 2489 patients, 36 (1.4%) were found to have AFLD by X-ray and/or CT. The mean disease duration was 11.7 (7.1) years. Patients with AFLD were more likely to be male [28 (77.8%) vs 1321 (53.9%), P = 0.004], older [56.3 (10.5) years vs 44.8 (11.4) years, P < 0.001], heavy smokers [27 (79.4%) vs 1468 (60.9%), P = 0.028] and have had longer disease duration [17. 7 (9.7) years vs 11.6 (7) years, P = 0.001]. QuantiFERON positivity was higher in the AFLD group [9 (36%) vs 309 (16.1%), P = 0.013]. While treatment with adalimumab was less preferred in those with AFLD, treatment with etanercept was more frequently preferred. CONCLUSION: As the radiological findings of AFLD can be confused with those of tuberculosis, special attention should be paid to differentiating between tuberculosis and the disease in males and in patients who have had long disease duration.

Do the drug doses of conventional synthetic DMARDs used for the treatment of biologic/targeted-synthetic DMARDs naive rheumatoid arthritis patients affect QuantiFERON-TB Gold Plus test results?

We aimed to obtain the effects of immunosuppressive doses on the QuantiFERON-TB Gold Plus (QFT-Plus) test results in Rheumatoid Arthritis (RA) patients. Besides this, the impact of the TB2 tube in QFT-Plus test was also investigated. This study included RA patients registered to HURBIO and were screened via QFT-Plus test for latent tuberculosis between January 2018 and March 2021, before the initiation of treatment of biologic/targeted-synthetic disease modifying anti-rheumatismal drugs (b/ts-DMARDs). Patients using methotrexate ≥ 10 mg or leflunomide (any dose) or steroids (≥ 7.5 mg prednisolone) at the time of QFT-Plus test were classified as the "high dose" group and the rest of the patients constituted the "low dose" group. The study included 534 RA patients; 353 [66.1%] in the high-dose group and 181 [33.9%] in the low-dose group. While QFT-Plus test was positive in 10.5% (37/353) patients in the high-dose group, it was positive in 20.4% (37/181) patients in the low-dose group (p < 0.001). The percentage of QFT-Plus indeterminate results were similar (around 2%) in both groups. The contribution of the TB2 tube to QFT-Plus test positivity was 6.89%. During a median (inter-quartile range) follow-up period of 23 (7-38) months under treatment of b/ts-DMARDs, latent TB reactivation was not observed. Primer active tuberculosis disease developed in two patients. Positive test results of Interferon-Gamma Release Assays (IGRAs) could decrease as immunosuppressive treatment doses increase in patients with RA and addition of the TB2 tube could increase test sensitivity.

Extremely high erythrocyte sedimentation rate revisited in rheumatic diseases: a singlecenter experience.

BACKGROUND: The objectives were to define the distribution of rheumatic diseases in patients with erythrocyte sedimentation rate (ESR) ≥ 100 mm/h and to find variables that can differentiate main study groups from others. METHODS: Charts of patients admitted with ESR ≥ 100 mm/h between 2015 and 2020 were reviewed. Patients were divided into four diagnostic groups based on etiology: infection (without a rheumatic diagnosis), oncologic (without a rheumatic diagnosis), rheumatic, and no definitive diagnosis. Patients with the rheumatic diagnosis were divided into three main study groups: those who had been recently diagnosed with a rheumatic disease, those who had a flare-up of the rheumatic disease, and those who had an infection in the course of the rheumatic disease. Appropriate statistical tests and decision-tree analysis by R and ROC curve were applied. p < 0.05 was considered statistically significant. RESULTS: A total of 2442 patients (311 (12.7%) with rheumatic disorders) were identified. Eightysix (27.7%) patients had newly diagnosed rheumatic disease (41; 47.7% with vasculitis); 111 (35.7%) had rheumatic disease flare-up (92; 82.9% with inflammatory arthritis); and 114 (36.6%) had coexisting infection (61; 53.5% inflammatory arthritis). Irrespective of the study group, the most commonly encountered diseases were rheumatoid arthritis and spondyloarthritis. Serum albumin levels (2.78 mg/dL) and platelet count (290/mm6 ) were valuable to discriminate disease flare-up and coexisting infection; moreover, high ferritin levels were accounted for adult-onset Still disease among patients with newly diagnosed rheumatic diseases. DISCUSSION: Extremely high ESR is still a valuable clinical parameter, and rheumatic causes are significant besides malignancy and infections. Albumin, thrombocyte count, and ferritin are other tests that clinicians should consider when caring for a patient with ESR ≥ 100 mm/h who has rheumatic disease.

Computed tomography imaging-based radiologic evaluation of pulmonary artery thrombosis in a series of patients with Behcet's disease.

AIM: Pulmonary artery involvement is a severe complication of Behcet's disease (BD). Although venous thrombosis is common in BD, pulmonary embolism is considered to be rare because the inflammatory nature makes the thrombi strongly adherent to the venous walls. This study aimed to define the radiological characteristics of pulmonary artery thrombosis (PAT) on computed tomography (CT) imaging in BD patients. METHODS: We retrospectively evaluated 165 BD patients with vascular involvement. Among the patients with venous involvement (n = 146), we identified 65 patients who had undergone thorax CT imaging previously. Fourteen patients who were diagnosed with PAT were included in the study. Expert radiologists re-evaluated the patients' initial and control thorax CT scans, classified the PAT as acute or chronic based on their radiological features. RESULTS: The patients' median age was 35 (min-max: 15-60) years at the time of the initial CT scan, and nine were male. Twelve (85.7%) patients were symptomatic at the time of CT evaluation. Upon re-evaluating the thorax CTs, acute PAT was diagnosed in six (42.8%); chronic PAT was detected in eight (57.1%) patients. Two patients with chronic PAT also had acute PAT. Pulmonary artery aneurysms were present in three (21.4%) patients, and intracardiac thrombus was found in three (21.4%) patients. CONCLUSION: A significant number of BD patients with venous involvement had radiological findings consistent with acute PAT potentially due to pulmonary emboli in this study. The clinical importance of these lesions has to be defined with future studies.

Factors that predict development of chronic kidney disease in patients with rheumatoid arthritis receiving biologic DMARDs and mortality rates.

OBJECTIVES: We aimed to determine the choice of biologic/targeted synthetic disease-modifying anti-rheumatic drugs (b/ts-DMARDs), factors associated with the development of chronic kidney disease (CKD), and mortality in RA patients with CKD receiving b/ts-DMARDs. METHODS: Two thousand one hundred forty-one RA (79.4% female) patients were included in the analysis from the HUR-BIO prospective registry. Patients were divided into the CKD group and the non-CKD group. Age and gender-matched patients were selected from the non-CKD group, and then three main groups were determined. CKD was staged according to the glomerular filtration rate criteria. The clinical characteristics of the patients, disease activities, treatment choices, drug retention rate, and mortality rates were compared between the groups. RESULTS: CKD was detected in 90/2141 (4.2%) RA patients on b/ts-DMARDs. Forty patients (2.3%) developed CKD during follow-up after the initiation of b/ts-DMARDs. In the CKD group, anti-TNF agents were chosen as the first-line b/ts-DMARDs therapy in 64.4% of patients, with etanercept leading in 31 (34.4%) patients. In multivariate analysis, age at the start of treatment, DAS-28-ESR at last visit, amyloidosis, hypertension, and history of smoking were the factors associated with the development of CKD in RA patients receiving b/ts-DMARDs. The mortality rate in RA-CKD patients until the onset of the pandemic was 15.41 per 1000 patient years, whereas it was 85.9 per 1000 patient years after the pandemic. CONCLUSION: Comorbidities and control of disease activity are critical in the development of CKD in RA patients receiving b/ts-DMARDs. While there was no significant difference in mortality rate between CKD and non-CKD patients, the overall mortality rate increased after the COVID-19 pandemic duration in both groups.

Unveiling cancer risk in ANCA-associated vasculitis: result from the Turkish Vasculitis Study Group (TRVaS).

To investigate cancer incidence in patients with ANCA-associated vasculitis (AAV), compare it with the age/sex-specific cancer risk of the Turkish population, and explore independent risk factors associated with cancer. This multicenter, incidence case-control study was conducted using the TRVaS registry. AAV patients without cancer history before AAV diagnosis were included. Demographic and AAV-related data of patients with and without an incident cancer were compared. Standardized cancer incidence rates were calculated using age-/sex-specific 2017 Turkish National Cancer Registry data for cancers (excluding non-melanoma skin cancers). Cox regression was performed to find factors related to incident cancers in AAV patients. Of 461 AAV patients (236 [51.2%] male), 19 had incident cancers after 2022.8 patient-years follow-up. Median (IQR) disease duration was 3.4 (5.5) years, and 58 (12.6%) patients died [7 with cancer and one without cancer (log-rank, p = 0.04)]. Cancer-diagnosed patients were older, mostly male, and more likely to have anti-PR3-ANCA positivity. The cumulative cyclophosphamide dose was similar in patients with and without cancer. Overall cancer risk in AAV was 2.1 (SIR) ((1.3-3.2), p = 0.004); lung and head-neck [primary target sites for AAV] cancers were the most common. In Cox regression, male sex and ≥ 60 years of age at AAV diagnosis were associated with increased cancer risk, while receiving rituximab was associated with decreased cancer risk. Cancer risk was 2.1 times higher in AAV patients than the age-/sex-specific cancer risk of the Turkish population population, despite a high rate of rituximab use and lower dose of cyclophosphamide doses. Vigilance in cancer screening for AAV patients covering lung, genitourinary, and head-neck regions, particularly in males and the elderly, is vital.

Hematologic Malignancy Risk in Inflammatory Arthritis Patients Treated with TNF Inhibitors: The Real-Life Data from the HUR-BIO Registry.

INTRODUCTION: This study aimed to assess the incidence of hematologic malignancy (HM) among inflammatory arthritis (IA) patients receiving tumor necrosis factor inhibitors (TNFi) compared with the general Turkish population. METHODS: HUR-BIO (Hacettepe University Rheumatology Biologic Registry) is a single-center biological disease-modifying anti-rheumatic drug (bDMARD) registry since 2005. Patients with IA, including rheumatoid arthritis, spondyloarthritis, or psoriatic arthritis who had at least one visit after the TNFi were screened from 2005 to November 2021. Standardized incidence rates (SIR) were calculated after adjustment for age and gender and compared with the 2017 Turkish National Cancer Registry (TNCR). RESULTS: Of the 6139 patients registered in the HUR-BIO, 5355 used any TNFi at least once. The median follow-up duration was 2.6 years for patients receiving TNFi. Thirteen patients developed a HM on follow-up. In these patients, the median age at the IA onset was 38 (range, 26-67), and the median age at the HM diagnosis was 55.5 (range, 38-76). Patients using TNFi had an increased HM incidence (SIR 4.23, 95% confidence interval (CI) 2.35-7.05). Ten patients with HM were under 65 years of age. In this group, there was a higher incidence of HM in both men (SIR 5.15, 95% CI 1.88-11.43) and women (SIR 4.76, 95% CI 1.74-10.55). CONCLUSIONS: The risk of HMs in inflammatory arthritis patients receiving TNFi was four times higher than in the general Turkish population.

Anxiety levels before biologic initiation and changes with treatment in patients with psoriatic arthritis: HUR-BIO biologic registry results.

OBJECTIVES: Psoriatic arthritis (PsA) is an inflammatory musculoskeletal disease related to several comorbidities. Anxiety is an important comorbidity in PsA and the data is scarce. We aimed to understand the rates before biologic agents and change in anxiety with the treatment. METHODS: PsA patients from the Hacettepe University biologic database (HUR-BIO) were assessed for the high anxiety level (score ≥ 4) using the patient self-reported measure of anxiety on a 0-10 numerical scale, included in the Psoriatic Arthritis Impact of Disease questionnaire (PSAID-12). The rate and scores of anxiety were determined before starting biologic agents, at the first visit within 6 months. Changes in anxiety scores were assessed according to favorable treatment responses, and the correlation was evaluated by Spearman correlation analysis. RESULTS: From 520 patients registered, 147 [mean (SD) age 43.3 (12.4) years, 70.7% female] had anxiety score both at baseline and first visit within 6 months. Both the frequency of high anxiety level and mean (SD) scores decreased at the first visit [63.9% vs. 41.4%, 4.8 (3.4) vs. 3.2 (3.1) respectively, p < 0.001 for both] after a mean (SD) follow-up of 105.7 (22.2) days. There was also a positive correlation between the change in anxiety scores and all parameters tested for treatment response: pain, PGA, BASDAI, HAQ-DI, DAS-28, and also PsAID-12. CONCLUSION: Anxiety is a more frequent problem at biologic initiation than rates observed in the general PsA population. The rates show a decreasing trend and correlates with treatment response but is still high within 6 months under treatment. KEY POINTS: • As high as 65% of patients had a high anxiety levels before the initiation of bDMARDs. • The disease activity control is essential in reducing anxiety; however, rates are still high within 6 months. • Decreased anxiety scores and rates of the high anxiety level are linked to better outcomes.

Anti-inflammatory and anti-apoptotic effect of nesfatin-1 on liver ischemia-reperfusion injury.

INTRODUCTION: Severe local and systemic tissue injury develop during reperfusion, which is a period during which arterial blood flow and tissue oxygenation are re-established. In this study, we aimed to investigate the anti-inflammatory, antioxidant and protective effects of nesfatin in IR damage developing in liver. MATERIAL AND METHODS: Twenty-four male Wistar-Albino rats were divided to three groups which contained eight rats in all groups. The rats were subjected to 30 minutes of hepatic pedicule occlusion followed by 2h of reperfusion to induce I/R damage. Nesfatin1 (10 µg/ kg) was administered, 30 min prior to ischemia and immediately before the reperfusion period. RESULTS: The findings showed that while the blood levels of AST, ALT and LDH were markedly elevated in the I/R group, they returned to normal levels upon treatment in the Nesfatin group. While IL-1 α, IL-1ß, IL-6, TNF-α and IFN- γ levels in blood and tissue were lower after therapy in the Nesfatin group compared to the I/R group, statistically significant decreases were only noted in IL-1ß, IL-6, TNF-α and IFN- γ levels. TAS levels increased in the treatment group, while upon nesfatin treatment statistically significant decreases were noted in TOS and OSI levels. Histopathological investigations also showed statistically significant decreases in Bax and Caspase-3 staining intensity and the number of stained cells in the Nesfatin group. CONCLUSION: The nesfatin has antioxidant activity and anti-inflammatory effect on improvement of liver functions and histopathological findings in liver ischemia and reperfusion injury. KEY WORDS: Anti-inflammatory, Anti apoptotic Liver ischemia-reperfusion injury, Nesfatin-1.

Ex situ Liver Resection and Partial Liver Autotransplantation for Advanced Cholangiocarcinoma.

Surgery is the only known curative treatment option for cholangiocarcinoma. Ex situ liver surgery and autotransplantation are promising approaches in cases that cannot be treated by conventional methods and particularly in the presence of centrally localized liver tumors as well as tumors that invade the main vascular structures. A 53-year-old female patient presented with abdominal pain and nausea. Abdominal tomography showed a tumoral mass lesion that filled the left lobe of the liver and invaded the left hepatic vein and the inferior vena cava. Cholangiocarcinoma diagnosis was reached based on biopsy findings, and the patient was scheduled for surgery as positron emission tomography did not indicate any other disease focus. The patient underwent ex situ liver resection and autotransplantation. She was discharged on the 7th postoperative day. A 68-year-old male presented with abdominal pain, weakness, and weight loss. Laboratory analysis indicated elevated carbohydrate antigen 19-9: 400 U/ml and alpha-fetoprotein (AFP): 2000 U/ml, and there was no other pathology. Abdominal tomography showed a mass that filled the center of the liver and invaded the left hepatic vein and the inferior vena cava. Pathological findings of the biopsy sample were reported as combined hepatocellular-cholangiocellular carcinoma. The patient's AFP levels continued to increase despite transcatheter arterial chemoembolization and radiofrequency ablation therapy. Surgery was decided as indocyanine green clearance test, and the result was 8.5%. He underwent ex situ liver resection and autotransplantation. Unfortunately, he died on the 4th postoperative day due to respiratory failure. Ex vivo liver resection and partial liver autotransplantation should be considered for the surgical treatment of locally advanced cholangiocarcinomas that invaded the main vascular structures.

Alternative hepatic arterial reconstruction technique in a case of total pancreaticoduodenectomy after celiac artery resection in pancreas cancer: Iliac-hepatic bypass.

Surgery is the only treatment method in pancreatic cancer. Unfortunately, metastatic diseases or invasion of the main vascular structures are observed in a majority of cases at the time of diagnosis; these structures originate from the body, neck, and tail of the pancreas and are considered inoperable. The first celiac artery resection for the treatment of cancer was described by Appleby in 1953. Here, we describe our hepatic artery reconstruction technique in a case with pancreatic body cancer. A 37-year-old male patient was admitted to our emergency department due to syncope. The patient was diagnosed with acute renal failure secondary to fluid loss. Thereafter, his general condition was stable and laboratory results improved. Abdominal computed tomography was performed. Pancreatic cancer originating from the pancreatic body was detected. A pancreatic biopsy was performed and neoadjuvant gemcitabine and paclitaxel chemoradiotherapy were initiated. Surgical treatment was recommended for the identification of regression after neoadjuvant chemoradiotherapy. Following intraoperative Doppler ultrasonography, en bloc distal pancreatectomy and splenectomy involving the celiac artery trunk and total gastrectomy were performed. However, surgical margin reliability in frozen section revealed that the tumor was still present. Therefore, the surgical procedure was replaced with total pancreaticoduodenectomy. Hepatic artery reconstruction was performed from the left main iliac artery using a 4-mm ringed GORE-TEX® graft. The iliac-hepatic bypass for hepatic artery reconstruction in pancreatic cancer could be an alternative surgical technique.

Rare Forms of Castleman Disease Mimicking Malignancy: Mesenteric and Pancreatic Involvement.

Castleman disease is a lymphoproliferative disorder with unknown etiology and pathogenesis. While the disease may involve all parts of the body, the mediastinum appears to be the most common part of involvement. In this study, we present two cases of Castleman disease with different localizations that mimicked malignancy. A 62-year-old female patient presented with jaundice. Laboratory analysis indicated aspartate aminotransferase: 250 U/L, total bilirubin: 4 mg/dl, and carbohydrate antigen (CA) 19-9: 900 U/ml. Computerized tomography (CT) of the abdomen showed a mass originating from the pancreas head which resulted in a biliary tract obstruction. A positron emission tomography-computed tomography (PET/CT) showed that the only site of involvement was the pancreas head. A decision was made to perform pancreaticoduodenectomy. During intra-abdominal exploration, lymphadenopathies were identified in the surroundings of the retropancreatic portal vein and the hepatic artery. Histopathological investigation of the dissected lymph nodes demonstrated findings consistent with granulomatous plasma-cell-rich Castleman disease. A 55-year-old female patient presented with abdominal pain, nausea, and vomiting. Computerized tomography of the abdomen showed an abdominal mass of 7 cm, originating from the mesenterium, with high-contrast uptake in the mesenterium in the lower abdominal quadrant. The mesenteric mass was resected along with segmentary small intestine resection. Histopathological investigation of the mass showed a giant granulomatous structure that consisted of plasma cells consistent with Castleman disease. Castleman disease should be kept in mind during differential diagnosis of locally advanced lymph nodes observed during preoperative investigations and intraoperative exploration.

An Alternative Technique in the Control of Massive Presacral Rectal Bleeding: Fixation of GORE-TEX® Aortic Patch.

The presacral venous system is located under the pelvic fascia covering the anterior of the sacrum and consists of two lateral sacral veins, middle sacral vein, and the veins that communicate them. The presacral venous system can be easily damaged and causes serious bleeding which is difficult to control and may cause intraoperative mortality. Its incidence varies between 3% and 9.4%. Although several methods have been tried to control presacral bleeding, the definitive method of treatment has not yet been identified. We present here our alternative technique in control of massive presacral massive bleeding developed from the presacral plexus secondary to the traction of the specimen during the dissection. The bleeding could not be controlled despite the use of all technical possibilities such as packing, ligation, and hemostatic agents. Bleeding control was provided by GORE-TEX® graft. We conclude that fixation of GORE-TEX® aortic patch should be kept in mind for uncontrolled massive presacral bleeding.

Avulsion of Ampulla of Vater Secondary to a Blunt Abdominal Injury Treated with Pancreatoduodenectomy; A Case Report and Literature Review.

The incidence of complex hepatobiliary injury secondary to blunt abdominal injuries varies between 3.4 and 5%. A 25-year old male patient underwent an urgent operation due to a motorcycle accident. During intraabdominal exploration, Grade 4 laceration was detected at the liver and bleeding was controlled through primary repair. In the postoperative seventh day, he was referred due to 1500 cc bile leakage from the drainage tube. During the operation, an extensive Kocher maneuver was done and the second part of duodenum was observed to be exposed to total avulsion from the head of the pancreas. Pancreatoduodenectomy was planned due to presence of ischemic changes in the second part of duodenum. In the postoperative follow-up, the abdomen was closed with a controlled abdominal closure procedure. The clinical findings of biliary tract injuries secondary to blunt abdominal injuries often manifest themselves late and early diagnosis is possible only with suspicion.

Alternative hepatic arterial reconstruction technique in case of total pancreaticoduodenectomy after celiac artery resection in pancreas cancer: Iliac-hepatic bypass.

Surgery is the only treatment method in pancreatic cancer. Unfortunately, metastatic diseases or invasion of the main vascular structures are observed in a majority of cases at the time of diagnosis; these structures originate from the body, neck, and tail of the pancreas and are considered inoperable. The first celiac artery resection for the treatment of cancer was described by Appleby in 1953. Here, we describe our hepatic artery reconstruction technique in a case with pancreatic body cancer. A 37-year-old male patient was admitted to our emergency department owing to syncope. The patient was diagnosed with acute renal failure secondary to fluid loss. Thereafter, his general condition was stable and laboratory results improved. Abdominal computed tomography was performed. Pancreatic cancer originating from the pancreatic body was detected. A pancreatic biopsy was performed and neoadjuvant gemcitabine and paclitaxel chemoradiotherapy were initiated. Surgical treatment was recommended for the identification of regression after neoadjuvant chemoradiotherapy. Following intraoperative Doppler ultrasonography, en bloc distal pancreatectomy and splenectomy involving the celiac artery trunk and total gastrectomy were performed. However, the surgical margin reliability in a frozen section revealed that the tumor was still present. Therefore, the surgical procedure was replaced with total pancreaticoduodenectomy. The hepatic artery reconstruction was performed from the left main iliac artery using a 4-mm ringed GORE-TEX® graft. The iliac-hepatic bypass for hepatic artery reconstruction in pancreatic cancer could be an alternative surgical technique.